Formaldehyde → 2-Acetyl-3,8-dimethyl-8-azabicyclo[3.2.1]oct-2-ene

HRID 483784Notes

Reaction equation

HRID 483784 reaction equation
[C:1]([C:4]1[CH:5]2[NH:12][CH:8]([CH2:9][C:10]=1[CH3:11])[CH2:7][CH2:6]2)(=[O:3])[CH3:2].C=O.[C:15]([BH3-])#N.[Na+].[OH-].[NH4+]>C(#N)C.C(O)(=O)C>[C:1]([C:4]1[CH:5]2[N:12]([CH3:15])[CH:8]([CH2:9][C:10]=1[CH3:11])[CH2:7][CH2:6]2)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 14923Ammonium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 197513562-Acetyl-3-methyl-8-azabicyclo[3.2.1]oct-2-ene

Product 1

HCID 190988202-Acetyl-3,8-dimethyl-8-azabicyclo[3.2.1]oct-2-ene

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-acetyl-3-methyl-8-azabicyclo[3.2.1]oct-2-ene (1.2083 g, 0.0073 mol) and aqueous formaldehyde (2.7 ml, 0.036 mol, 37 percent) in 15 ml acetonitrile was added sodium cyanoborohydride (0.7352 g, 0.0117 mol). After stirring for 15 minutes, the reaction was made acidic by addition of 15 ml glacial acetic acid over a 45 minute period. The solution was made basic by the addition of an aqueous solution of ammonium hydroxide. The basic solution was extracted 3 times with ethyl acetate, the organic layer was then dried using sodium sulfate and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography (using 9 parts diethyl ether and 1 part triethylamine) followed by bulb-to-bulb distillation (80° C. (0.4 mmHg)) to give 2-acetyl-3,8-dimethyl-8-azabicyclo[3.2.1]oct-2-ene as a brownish liquid.

Workup

  1. extractionThe basic solution was extracted 3 times with ethyl acetate
  2. customthe organic layer was then dried
  3. concentrationconcentrated under reduced pressure
  4. customThe concentrated residue was purified by silica gel column chromatography (using 9 parts diethyl ether and 1 part triethylamine)
  5. distillationfollowed by bulb-to-bulb distillation (80° C. (0.4 mmHg))

Sources & evidence

ORD record
ord-c61d415aec024c87876fdb39720438b1
Source dataset
uspto-grants-1993_07
Patent number
US05227385

Reaction notes

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